The goal of this research program is the application of optical biopsy techniques to the identification of adenomatous polyps in the colon. Specific optical instrumentation and software will be developed for this task. Spectroscopic detection of dysplasia has been demonstrated, and is accepted. It has been shown to be sensitive and selective, especially if the tissue volume being sampled is confined to the mucosal layer. For this reason, we propose a technique similar to confocal microscopy, which we Volume MicroProbe microscopy. This optical technique is ideally suited for operation through the working channel of a typical colonoscope. Clinical trials with human subjects are included in the application. PROPOSED COMMERCIAL APPLICATION: Colorectal cancer claims approximately 60,000 individuals in the US annually. It is a highly curable disease if detected in its early stages. The proposed optical biopsy instrumentation will improve diagnostic capability and may modify current practice of removing small benign hyperplastic polyps which are indistinguishable from precancerous polyps. Therefore, the commercial potential is high, especially considering that approximately 15.5M colonoscopes and sigmoidoscopies are performed in the US each year. If even 10% of these procedures include an optical biopsy, the number of optical procedures will be over 1.6M annually.